The geriatric distal femur fracture: nail, plate or both?

Surgical fixation of distal femur fractures in geriatric patients is an evolving topic. Unlike hip fractures, treatment strategies for distal femur fractures are ill-defined and lack substantive high-quality evidence. With an increasing incidence and an association with significant morbidity and mortality, it is essential to understand existing treatment options and their supporting evidence. Current fixation methods include the use of either retrograde intramedullary nails, or plate and screw constructs. Due to the variability in fracture patterns, the unique anatomy of the distal femur, and the presence or absence or pre-existing implants, decision-making as to which method to use can be challenging. Recent literature has sought to describe the advantages and disadvantages of each, however, there is currently no consensus on a standard of care, and little randomized evidence is available that directly compares intramedullary nails with plating. Future randomized studies comparing intramedullary nails with plating constructs are necessary in order to develop a standard of care based on injury characteristics.

Single-cell analysis of embryoid body heterogeneity using microfluidic trapping array.

The differentiation of pluripotent stem cells as embryoid bodies (EBs) remains a common method for inducing differentiation toward many lineages. However, differentiation via EBs typically yields a significant amount of heterogeneity in the cell population, as most cells differentiate simultaneously toward different lineages, while others remain undifferentiated. Moreover, physical parameters, such as the size of EBs, can modulate the heterogeneity of differentiated phenotypes due to the establishment of nutrient and oxygen gradients. One of the challenges in examining the cellular composition of EBs is the lack of analytical methods that are capable of determining the phenotype of all of the individual cells that comprise a single EB. Therefore, the objective of this work was to examine the ability of a microfluidic cell trapping array to analyze the heterogeneity of cells comprising EBs during the course of early differentiation. The heterogeneity of single cell phenotype on the basis of protein expression of the pluripotent transcription factor OCT-4 was examined for populations of EBs and single EBs of different sizes at distinct stages of differentiation. Results from the cell trap device were compared with flow cytometry and whole mount immunostaining. Additionally, single cells from dissociated pooled EBs or individual EBs were examined separately to discern potential differences in the value or variance of expression between the different methods of analysis. Overall, the analytical method described represents a novel approach for evaluating how heterogeneity is manifested in EB cultures and may be used in the future to assess the kinetics and patterns of differentiation in addition to the loss of pluripotency.

Alginate encapsulation parameters influence the differentiation of microencapsulated embryonic stem cell aggregates.

Pluripotent embryonic stem cells (ESCs) have tremendous potential as tools for regenerative medicine and drug discovery, yet the lack of processes to manufacture viable and homogenous cell populations of sufficient numbers limits the clinical translation of current and future cell therapies. Microencapsulation of ESCs within microbeads can shield cells from hydrodynamic shear forces found in bioreactor environments while allowing for sufficient diffusion of nutrients and oxygen through the encapsulation material. Despite initial studies examining alginate microbeads as a platform for stem cell expansion and directed differentiation, the impact of alginate encapsulation parameters on stem cell phenotype has not been thoroughly investigated. Therefore, the objective of this study was to systematically examine the effects of varying alginate compositions on microencapsulated ESC expansion and phenotype. Pre-formed aggregates of murine ESCs were encapsulated in alginate microbeads composed of a high or low ratio of guluronic to mannuronic acid residues (High G and High M, respectively), with and without a poly-L-lysine (PLL) coating, thereby providing four distinct alginate bead compositions for analysis. Encapsulation in all alginate compositions was found to delay differentiation, with encapsulation within High G alginate yielding the least differentiated cell population. The addition of a PLL coating to the High G alginate prevented cell escape from beads for up to 14 days. Furthermore, encapsulation within High M alginate promoted differentiation toward a primitive endoderm phenotype. Taken together, the findings of this study suggest that distinct ESC expansion capacities and differentiation trajectories emerge depending on the alginate composition employed, indicating that encapsulation material physical properties can be used to control stem cell fate.

Stem cell microencapsulation for phenotypic control, bioprocessing, and transplantation.

Cell microencapsulation has been utilized for decades as a means to shield cells from the external environment while simultaneously permitting transport of oxygen, nutrients, and secretory molecules. In designing cell therapies, donor primary cells are often difficult to obtain and expand to appropriate numbers, rendering stem cells an attractive alternative due to their capacities for self-renewal, differentiation, and trophic factor secretion. Microencapsulation of stem cells offers several benefits, namely the creation of a defined microenvironment which can be designed to modulate stem cell phenotype, protection from hydrodynamic forces and prevention of agglomeration during expansion in suspension bioreactors, and a means to transplant cells behind a semi-permeable barrier, allowing for molecular secretion while avoiding immune reaction. This review will provide an overview of relevant microencapsulation processes and characterization in the context of maintaining stem cell potency, directing differentiation, investigating scalable production methods, and transplanting stem cells for clinically relevant disorders.

Preoperative Comorbidities Associated With Early Mortality in Hip Fracture Patients: A Multicenter Study.

OBJECTIVE: Multiple comorbidities in hip fracture patients are associated with increased mortality and complications. The goal of this study was to characterize the relationship between specific patient factors including comorbidities and outcomes in geriatric hip fractures, including length of stay, unplanned ICU admission, discharge disposition, complications, and mortality. METHODS: This is a retrospective review of a trauma database from five Level 1 and Level 2 trauma centers of patients with hip fractures of the femoral neck and intertrochanteric region who underwent treatment using hip pinning, hemiarthroplasty, total hip arthroplasty, cephalomedullary nailing, or dynamic hip screw fixation. Mortality was the primary outcome variable (including in-hospital mortality, 30-day mortality, 60-day mortality, and 90-day mortality). Secondary outcome variables included in-hospital adverse events, unplanned transfer to the ICU, postoperative length of stay, and discharge disposition. Regression analyses were used for evaluation of relationships between comorbidities as independent variables and primary and secondary outcomes as dependent variables. RESULTS: Two thousand three hundred patients were included. The mortality was 1.8%, 7.0%, 10.9%, and 14.1% for in-hospital, 30-day, 60-day, and 90-day mortality, respectively. Diabetes and cognitive impairment present on admission were associated with mortality at all-time intervals. COPD was the only comorbidity that signaled in-hospital adverse event with an odds ratio of 1.67 (P = 0.012). No patient factors, time to surgery, or comorbidities signaled unplanned ICU transfer. Patients with renal failure and COPD had longer hospital stays after surgery. CONCLUSION: Geriatric hip fractures continue to have high short-term morbidity and mortality. Identifying patients with increased odds of early mortality and adverse events can help teams optimize care and outcomes. Patients with diabetes, cognitive impairment, renal failure, and COPD may benefit from continued and improved medical optimization during the perioperative period as well as being more closely managed by a medicine team without delaying time to the operating room.

Intramedullary Nail for a Distal Tibia Fracture.

Extraarticular fractures of the distal tibia have historically been treated with open reduction and fixation with plates and screws. This technique requires a more extensive dissection and comes with a higher risk of wound complications than intramedullary nail fixation. This article and the accompanying video demonstrate the use of closed reduction and suprapatellar nail fixation appropriate for the treatment of most extraarticular distal tibial fractures. A variety of treatment decisions are discussed, including the nail insertion method, fixation of associated fibular fractures, and postoperative immobilization.

Effects of prolonged lung inflation or deflation on pulmonary stretch receptor discharge in the alligator (Alligator mississippiensis).

The American alligator (Alligator mississippiensis) is a semi-aquatic diving reptile that has a periodic breathing pattern. Previous work identified pulmonary stretch receptors, that are rapidly and slowly adapting, as well as intrapulmonary chemoreceptors (IPC), sensitive to CO2, that modulate breathing patterns in alligators. The purpose of the present study was to quantify the effects of prolonged lung inflation and deflation (simulated dives) on pulmonary stretch receptors (PSR) and/or IPC discharge characteristics. The effects of airway pressure (0-20 cm H2O), hypercapnia (7% CO2), and hypoxia (5% O2) on dynamic and static responses of PSR were studied in juvenile alligators (mean mass=246 g) at 24°C. Alligators were initially anesthetized with isoflurane, cranially pithed, tracheotomized and artificially ventilated. Vagal afferent tonic and phasic activity was recorded with platinum hook electrodes. Receptor activity was a mixture of slowly adapting PSR (SAR) and rapidly adapting PSR (RAR) with varying thresholds and degrees of adaptation, without CO2 sensitivity. Receptor activity before, during and after 1 min periods of lung inflation and deflation was quantified to examine the effect of simulated breath-hold dives. Some PSR showed a change in dynamic response, exhibiting inhibition for several breaths after prolonged lung inflation. Following 1 min deflation, RAR, but not SAR, exhibited a significant potentiation of burst frequency relative to control. For SAR, the post-inflation receptor inhibition was blocked by CO2 and hypoxia; for RAR, the post-inflation inhibition was potentiated by CO2 and blocked by hypoxia. These results suggest that changes in PSR firing following prolonged inflation and deflation may promote post-dive ventilation in alligators. We hypothesize that PSR in alligators may be involved in recovery of breathing patterns and lung volume during pre- and post-diving behavior and apneic periods in diving reptiles.